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New pyridazine and pyridazinone derivatives 3a–g, 4a–f, 6a, and 6b were designed and synthesized. Cell viability of all compounds was established based on the viability of lipopolysaccharide‐induced RAW264.7 macrophage cells determined via the MTT assay. In vitro inhibition assays on human COX‐1 and COX‐2 enzymes were conducted to probe the newly synthesized compounds' anti‐inflammatory activity. The half maximal inhibitory concentration values for the most active compounds, 3d, 3e, and 4e towards COX‐2 were 0.425, 0.519, and 0.356 µM, respectively, in comparison with celecoxib. The newly synthesized compounds' ability to inhibit the production of certain proinflammatory cytokines, such as inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐6, and prostaglandin‐E2, was also estimated in lipopolysaccharide‐induced macrophages (RAW264.7 cells). Compounds 3d and 3e were identified as the most potent cytokine production inhibitors. The results of molecular modeling studies suggested that these compounds were characterized by a reasonable binding affinity toward the active site of COX‐2, when compared to a reference ligand. These results might be taken into consideration in further investigations into new anti‐inflammatory agents. [ABSTRACT FROM AUTHOR]

Heterocyclics containing pyridazinone and piperazine structures are potential anticancer agents in the treatment of cancer disease caused by increasing the number of abnormal cells disrupting body biochemistry. There is a need for the design of more biocompatible drugs for the treatment of cancer with minimal side effects. For this purpose, a series of piperazinyl‐methyl‐3(2H)pyridazinone based compounds were synthesized and their anticancer activities were studied in vitro and in silico. The chemical structures of all the new compounds 3 (a–k) were identified by spectral analysis. The new compounds were screened in human lung and colon cancer cell lines to learn about their cytotoxic effects. The importance of the structure activity relationship was seen in this study and the compounds containing methoxy groups on the phenyl ring (3 a, 3 b, 3 e–3 g) were found to have higher cytotoxic effects than those without. It was determined that one of these compounds (3 a) demonstrated significant cytotoxic effect against both cell lines for 72 h as in vitro. The geometry of the synthesized 3 a ligand was optimized using the hybrid B3LYP functional density functional theory (DFT). Molecular docking study of 3 a compound was performed against EGFR (PDB ID : 1M17) and VEGFR‐2 (PDB ID: 2RL5) molecular targets. [ABSTRACT FROM AUTHOR]

Pyridazinones are important nitrogen‐rich heterocyclic core that has been driving the substantial medicinal interest due to their wide range of biological activities. This privileged scaffold forms a central core in numerous potent compounds, which results in the development of novel anticancer drugs with fruitful biological activities. The current review article summarizes the progressive development of novel pyridazinone derivatives that are targets for numerous receptors such as C‐met kinase inhibitors, PARP inhibitors, Tubulin polymerization inhibitors, Dihydro folate reductase inhibitors, B‐Raf inhibitors, Bruton tyrosine kinase inhibitors, FER tyrosine kinase inhibitors, and fibroblast growth factors receptors. It features the various simple techniques for the synthesis of pyridazinones and also highlights the mechanistic insights into the anticancer properties of pyridazinone derivatives. [ABSTRACT FROM AUTHOR]

A series of novel (p‐chlorophenyl)‐3(2H)pyridazinone compounds were synthesized starting from p‐chloroacetophenone as AChE/BChE inhibitors. The chemical structures of all the compounds were identified by spectral analysis. Cholinesterase inhibition activity studies and in silico studies of compounds designed to eliminate the symptomatic effects of Alzheimer's disease and slow down neurodegeneration were evaluated. According to the results obtained, it was revealed that N‐substituted‐(p‐ chlorophenyl)pyridazin‐3(2H)‐one derivatives inhibited enzymes significantly. Ki values were found for acetylcholinesterase in the range of 10.2±4.0–20.9±7.6 nM and for butyrylcholinesterase in the range of 0.70±0.34–1.67±1.12 nM. Compound 5e showed the best effect on AChE activity compared to Tacrine. Also, compound 5b showed the best effect in BChE inhibition. The interactions of the synthesized compounds with the best experimental activities against AChE, BChE, respectively, were investigated by in silico approaches. In molecular docking, 5b compound with AChE crystal structure (PDB ID:1ACJ), binding site and binding parameters of 5e compound with BChE crystal structure were investigated in detail. The results indicated that compound 5b and 5e could be a promising lead compound for further development as a therapeutic agent for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In this study, a series of N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives were synthesized and evaluated for their AChE inhibitory activity. The chemical structures of novel compounds 5(a–m) were confirmed by 1H‐NMR, 13C‐NMR, IR and HRMS analysis. In order to eliminate the symptomatic effects of Alzheimer's disease, the proposed compounds were evaluated by acetylcholinesterase inhibition activity study in accordance with the cholinergic hypothesis. The results revealed that the N‐substituted‐(p‐tolyl)pyridazin‐3(2H)‐one derivatives inhibited the enzymes significantly. Ki values for acetylcholinesterase in the range of 0.56±0.15–4.12±1.42 μM. Compound 5 h demonstrated the greatest in AChE activity compared with tacrine (0.56±0.15 μM). Molecular docking studies were performed for all compounds that compared tacrine in AChE activity in‐vitro. As a result of molecular docking studies (ΔGBind, docking score, XP Gscore, Glide energy, Glide emodel), 5 f, 5 g and 5 h compounds showed good inhibitory properties in the AChE active site as in silico. [ABSTRACT FROM AUTHOR]

The first regio‐, diastereo‐, and enantioselective direct Mannich reaction of β,γ,‐unsaturated ketones with benzoxazinone cyclic imines was enabled by Lewis acid/Brønsted base cooperative catalysis. The dinuclear zinc complex catalyzed the reaction of a broad range of β,γ‐unsaturated ketones to proceed at the α‐site exclusively, leading to corresponding adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90–99 % ee range. These products were used as general intermediates in the synthesis of multisubstituted cyclocanalines, tetrahydro pyridazinones, and 4H‐furo[2,3‐b][1,4]benzoxazine derivatives. [ABSTRACT FROM AUTHOR]

The chemoselective reactions of 2‐(5‐mercapto‐4‐phenyl‐4H‐[1,2,4]triazol‐3‐ylmethyl)‐6‐p‐tolyl‐4,5‐dihydro‐2H‐pyridazin‐3‐one (3) with different electrophiles were evaluated. Triazole 3 reacted with alkyl halides in the presence of triethylamine in alcohol to give the corresponding S‐substituted derivatives. On the basis of S‐chemoselective reactions of triazole 3, a series of amino acid 10a–d and dipeptide derivatives 12a–d were prepared via azide coupling of the corresponding hydrazides 9 and 15 with amino acid ester hydrochlorides, respectively. N‐Substituted triazoles 6a–c or 7a–d attached to pyridazin‐3‐one moiety were successfully formed by the reaction of 3 with activated acrylic acid derivatives or with amines. Antibacterial activities of the synthesized derivatives were investigated through correlation with Escherichia coli FabH inhibitory activities using molecular modeling docking software. The antimicrobial activity of synthesized compounds was evaluated, showing best inhibition zone for N‐substituted carboxylic acid 5a and N‐substituted nitrile 5c parallel to the molecular modeling studies. [ABSTRACT FROM AUTHOR]

The reaction of 3‐oxo‐2‐arylhydrazonopropanals with ethyl cyanoacetate in acetic acid containing ammonium acetate was found to afford only 2‐amino‐5‐phenylazonicotinate 9 and not 2‐hydroxy‐6‐substituted‐5‐arylazonicotinates 6, as has been demonstrated by the obtained X‐ray data. Also, we found that the reaction 3‐oxo‐2‐arylhydrazonopropanals with ethyl cyanoacetate in ethanol containing triethylamine affords only the pyridazinone 11 and the obtained X‐ray data for this compound conclusively prove this structure. [ABSTRACT FROM AUTHOR]

Abstract: An efficient N‐arylation of pyridazinones with diaryliodonium salts has been developed without using base or metal catalysts. The reaction tolerated a variety of both diaryliodonium salts and pyridazinone derivatives with diverse functional groups. Furthermore, a drug candidate for treatment of neuropathic pain was synthesized with this procedure in good yield. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a leading cause of hospital-acquired infections in the USA and is a major health concern as methicillin-resistant S. aureus and other antibiotic-resistant strains are common. Compounds that inhibit the S. aureus sortase (SrtA) cysteine transpeptidase may function as potent anti-infective agents as this enzyme attaches virulence factors to the bacterial cell wall. While a variety of SrtA inhibitors have been discovered, the vast majority of these small molecules have not been optimized using structure-based approaches. Here we have used NMR spectroscopy to determine the molecular basis through which pyridazinone-based small molecules inhibit SrtA. These inhibitors covalently modify the active cysteine thiol and partially mimic the natural substrate of SrtA by inducing the closure of an active site loop. Computational and synthetic chemistry methods led to second-generation analogues that are ~70-fold more potent than the lead molecule. These optimized molecules exhibit broad-spectrum activity against other types of class A sortases, have reduced cytotoxicity, and impair SrtA-mediated protein display on S. aureus cell surface. Our work shows that pyridazinone analogues are attractive candidates for further development into anti-infective agents, and highlights the utility of employing NMR spectroscopy and solubility-optimized small molecules in structure-based drug discovery. [ABSTRACT FROM AUTHOR]

A class of pyridazinone derivatives as near-infrared optical probes in fluorescence microscopy images was designed. The design strategy consisted of the stepwise extension and modification of pyridazinone by expansion of the electron-donating moiety to a larger π-conjugated system and anchoring a subcellular directing group such as triphenylphosphine or morpholine. All the desired products were successfully applied in cell imaging with high subcellular colocalization. Furthermore, these fluorescent probes showed excellent performance in mouse-brain imaging. [ABSTRACT FROM AUTHOR]

The K-Ras GTPase is a major target in anticancer drug discovery. However, direct interference with signaling by K-Ras has not led to clinically useful drugs yet. Correct localization and signaling by farnesylated K-Ras is regulated by the prenyl binding protein PDEδ. Interfering with binding of PDEδ to K-Ras by means of small molecules provides a novel opportunity to suppress oncogenic signaling. Here we describe the identification and structure-guided development of novel K-Ras-PDEδ inhibitor chemotypes based on pyrrolopyridazinones and pyrazolopyridazinones that bind to the farnesyl binding pocket of PDEδ with low nanomolar affinity. We delineate the structure-property relationship and in vivo pharmacokinetic (PK) and toxicokinetic (Tox) studies for pyrazolopyridazinone-based K-Ras-PDEδ inhibitors. These findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic Ras. [ABSTRACT FROM AUTHOR]

A new method for the preparation of 2-substituted 6-chloro-2,7-dihydro-3 H-dibenzo[ de, h]cynnoline-3,7-diones has been developed. The compounds have been obtained in an original three-step procedure comprising the oxidation of 1-methyl-9,10-anthraquinones with periodate or permanganate/brominating reagent systems, to 6-chloro-2,7-dihydro-3 H-dibenzo[ de, h]cynnoline-3,7-dione, and selective thereof. The selected processes were applied in the efficient scale-up of specific 2,6-substituted 2,7-dihydro-3 H-dibenz[ de, h]cinnolin-3,7-dione derivatives, currently being investigated pre-clinically as anticancer agents. [ABSTRACT FROM AUTHOR]

A number of pyridazinone derivatives bearing substituted benzylidene and heterocyclic/aromatic rings at 4th and 6th positions, respectively were synthesized in good to moderate yields and screened for antioxidant activity. Antioxidant activity of pyridazinone derivatives was evaluated by using several in vitro radical scavenging methods such as 1,1-diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2), nitric oxide (NO), reducing power, and metal chelating assay etc. Molegro virtual docker software was used to study the binding affinity of the title compounds with the xanthine oxidoreductase enzyme. Amongst the tested compounds, 5a, 5d, 5g & 5j were found to exhibit excellent antioxidant activity at par with the positive control, ascorbic acid. The molecular docking studies of these compounds demonstrated a good selectivity profile with xanthine oxidoreductase receptors. A preliminary study of the structural-activity relationship showed that the presence of electron withdrawing group and heterocyclic ring on pyridazinone nucleus are associated with the best potency and selectivity profile. It could be proposed that xanthine oxidoreductase receptor may be involved in observed antioxidant activity of pyridazinone derivatives bearing aromatic ring and benzylidene substituents and thus the synthesized compounds are worthy of further exploration. [ABSTRACT FROM AUTHOR]

Some new 3-(alkylsulfanyl)-7-chloro-1-phenyl-1 H-pyridazino [4,3- e][1,3,4]thiadiazine were synthesized by treatment of the alkyl-2-phenylhydrazinecarbodithioates with 4-bromo-3,6-dichloropyridazine in alkaline acetonitrile. Orientation of the reaction has been determined by X-ray crystallography technique. The chlorine atom on the number 7 position of these products was replaced by secondary amines at reflux condition. [ABSTRACT FROM AUTHOR]

Phthalazinone derivatives were designed as optical probes for one- and two-photon fluorescence microscopy imaging. The design strategy involves stepwise extension and modification of pyridazinone by 1) expansion of pyridazinone to phthalazinone, a larger conjugated system, as the electron acceptor, 2) coupling of electron-donating aromatic groups such as N, N-diethylaminophenyl, thienyl, naphthyl, and quinolyl to the phthalazinone, and 3) anchoring of an alkyl chain to the phthalazinone with various terminal substituents such as triphenylphosphonio, morpholino, triethylammonio, N-methylimidazolio, pyrrolidino, and piperidino. Theoretical calculations were utilized to verify the initial design. The desired fluorescent probes were synthesized by two different routes in considerable yields. Twenty-two phthalazinone derivatives were synthesized and their photophysical properties were measured. Selected compounds were applied in cell imaging, and valuable information was obtained. Furthermore, the designed compounds showed excellent performance in two-photon microscopic imaging of mouse brain slices. [ABSTRACT FROM AUTHOR]

The reaction of 4-(4-acetylamino/bromophenyl)-4-oxobut-2-enoic acids with carbon nucleophiles afforded Michael adducts depending on the type of reagents and medium (acidic or basic). The adducts 2 and 3 were used as key starting materials to synthesize some heterocyclic compounds, which include pyridazinone, furanone, 1,2-oxazin-5-one, 1.2-diazapine, pyrane, and hydroxyl pyridine derivatives. The Steric factor plays an important role in regioselectivity. The structure of newly synthesized compounds was elucidated by elemental analysis and spectroscopic data. [ABSTRACT FROM AUTHOR]

RATIONALE: 5-Amino-4-chloro-2-phenyl-3(2H)-pyridazone (Chloridazon) is an important systemic herbicide; its transformation by different Advanced Oxidation Processes could result in the formation of different and complex products. These products, that need to be identified, may present a more toxic effect than the parent compound. METHODS: The exact and unequivocal structural characterization of the detected by-products of Chloridazon was performed by in-depth analysis of the liquid chromatography/negative electrospray ionization tandem mass spectrometric (LC/ESI+/MS²) fragmentation. Such a technique is a powerful and sensitive analytical tool to study environmental issues. The reactive radicals that induce the degradation of Chloridazon were generated by selective excitation of titanium dioxide as photocatalyst and also by UV photolysis of hydrogen peroxide. RESULTS: Several processes are initiated by hydroxyl radical reaction with Chloridazon. Among them (i) hydroxylation of the phenyl group at the ortho, meta and para positions; (ii) a second hydroxylation process as a secondary reaction is also obtained within the phenyl moiety; (iii) scission of the phenyl-N bond through a hydrolysis process; and (iv) a substitution of the chlorine atom by a hydroxyl group. CONCLUSIONS: LC/ESI-Q-TOFMS appeared to be a valuable and precise tool for structural elucidation of the unknown by-products that were generated during hydroxyl radical reactions with Chloridazon. Several hydroxylated and dihydroxylated isomers were identified together with dechlorinated and bridge opening products. [ABSTRACT FROM AUTHOR]

A continuous flow process delivering key building blocks for a series of BCP modulator libraries is reported. A dynamically mixed flow reactor emerged as a pivotal technology in both synthesis and isolation phases enabling the processing of slurries and suspensions while maintaining high productivity and reliability. Accordingly, the synthesis of common intermediates in flow were employed to further build a pyridazone-based library (36 compounds) aimed at improving lead compound potency and selectivity while further enabling structure-activity relationship studies of a new BCP modulator family. [ABSTRACT FROM AUTHOR]

The synthesis of chlorinated tetrahydropyridazin-3-ones and 1,2-diazepan-3-ones has been developed. The present paper describes the application of Cu(I)-catalyzed ATRC for the synthesis of heterocyclic molecules containing two heteroatoms (i.e., nitrogen) in the ring for the first time. An easy separation of the individual compounds from the product mixture could be achieved by considering their solubility/insolubility in n-hexane. The presence of three chlorine atoms provides possibilities for further derivatization. [ABSTRACT FROM AUTHOR]

Three new ureido-pyridazinone derivatives, which are structurally related to the known STAT3 inhibitor AVS-0288, were designed by taking into account the structure-activity relationships determined for several ureido-oxadiazole derivatives previously studied by our group. Their synthesis was first attempted through suitable 5-aminopyridazinone intermediates ( 6a and 6b), which molecular structures were confirmed by means of X-ray diffraction data on 6a. Amine functionalization was unsuccessful, therefore, an alternative method was devised. Dual-luciferase and AlphaScreen-based assays were used to test their activity. The obtained data were rationalized on the basis of a modeling study, which focused our attention on the geometrical preferences of the ureido moiety. Computational results seem to indicate that both the 1,2,5-oxadiazole ring and the extended ZZ arrangement are essential and probably act in a synergistic way to confer significant activity against STAT3. [ABSTRACT FROM AUTHOR]

This study reports the synthesis and characterization of 4-chloro-2- tert-butyl-5-[2-[[1-[2-[18F]fluroethyl]-1 H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2 H)-pyridazinone ([18F]Fmp2) for myocardial perfusion imaging (MPI). The tosylate precursor and non-radioactive compound [19F]Fmp2 were synthesized and characterized by infrared, 1H-NMR, 13C-NMR, and mass spectra (MS). The radiotracer [18F]Fmp2 was obtained by one-step nucleophilic substitution of tosyl with 18F, and evaluated as an MPI agent in vitro and in vivo. Starting from [18F]KF/K222 solution, the typical decay-corrected radiochemical yield (RCY) was 38 ± 8.8% with high radiochemical purity (>98%). The specific activity was calculated as 10 GBq/µmol at the end of synthesis determined by HPLC analysis. In the mice biodistribution, [18F]Fmp2 showed very high initial heart uptake (53.35 ± 5.47 %ID/g at 2 min after injection) and remarkable retention. The heart/liver, heart/lung, and heart/blood ratios were 7.98, 8.20, and 53.13, respectively at 2 min post-injection. In the Positron Emission Tomography (PET) imaging study of Chinese mini-swine, the standardized uptake value of the liver decreased modestly during the 2 h post-injection, while the heart uptake and heart/liver ratios continued to increase with time. [18F]Fmp2 exhibited good stability, high heart uptake and low lung uptake in mice and Chinese mini-swine. It may be worthy of further modification to improve liver clearance for MPI in the future. [ABSTRACT FROM AUTHOR]

Background and Purpose The Ca2+ sensitizer pimobendan is a unique inotropic agent that improves cardiac contractility with less of an increase in oxygen consumption and potentially fewer adverse effects on myocardial remodelling and arrhythmia, compared with traditional inotropes. However, clinical trials report contradictory effects of pimobendan in patients with heart failure ( HF). We provide mechanistic experimental evidence of the efficacy of pimobendan using a novel mouse model of progressive HF. Experimental Approach A knock-in mouse model of human genetic dilated cardiomyopathy, which shows a clear transition from compensatory to end-stage HF at a fixed time during growth, was used to evaluate the efficacy of pimobendan and explore the underlying molecular and cellular mechanisms. Key Results Pimobendan prevented myocardial remodelling in compensated HF and significantly extended life span in both compensated and end-stage HF, but dose-dependently increased sudden death in end-stage HF. In cardiomyocytes isolated from end-stage HF mice, pimobendan induced triggered activity probably because of early or delayed afterdepolarizations. The L-type Ca2+ channel blocker verapamil decreased the incidence of triggered activity, suggesting that this was from over-elevated cytoplasmic Ca2+ through increased Ca2+ entry by PDE3 inhibition under diminished sarcoplasmic reticulum Ca2+ reuptake and increased Ca2+ leakage from sarcoplasmic reticulum in end-stage HF. Conclusions and Implications Pimobendan was beneficial regardless of HF stage, but increased sudden cardiac death in end-stage HF with extensive remodelling of Ca2+ handling. Reduction of cytoplasmic Ca2+ elevated by PDE3 inhibition might decrease this risk of sudden cardiac death. [ABSTRACT FROM AUTHOR]

This research describes the utility of 4-(4-bromophenyl)-4-oxobut-2-enoic acid as a key starting material for preparation of a novel series of aroylacrylic acids, pyridazinones, and furanones derivatives. These heterocyclic compounds were synthesized by reaction of 4-(4-bromophenyl)-4-oxobut-2-enoic acid with benzimidazole, ethyl glycinate hydrochloride, anthranilic acid and o-phenylenediamine under Aza-Michael addition conditions. Every Aza-Michael adduct was allowed to react with haydrazine hydrate and to form pyridazinones and furanones derivatives, respectively. In further step, some pyridazinones were allowed to react with ethyl acetoacetate, acetyl acetone, , and aromatic aldehydes to form novel heterocylces. Finally, studying antibacterial activities of these compounds was performed. [ABSTRACT FROM AUTHOR]

A ruthenium-catalyzed switchable N-H/C-H alkenylation reaction of 6-phenyl-(dihydro)pyridazin-3(2 H)-ones triggered by a nitrogen/oxygen atmosphere was developed. To achieve switchable modification of the two important sites of the widely used pharmacophore, a simple and efficient procedure containing two optimized ruthenium catalytic systems was utilized, which afforded excellent activity, high selectivity, and good tolerance of a wide range of functional groups. [ABSTRACT FROM AUTHOR]

The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. [ABSTRACT FROM AUTHOR]

The copper-catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six-membered pyridazinones in the complete absence of five-membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2-halobenzaldehyde as the starting material, under identical reaction conditions, gave 6-(2-ethoxyphenyl)pyridazinones after sequential Michael addition/1,2-addition/Ullmann cross-coupling reactions. [ABSTRACT FROM AUTHOR]

A simple and efficient procedure for the synthesis of pyridazin-3(2 H)-ones through copper-catalyzed dehydrogenation of a single C-C bond of 4,5-dihydropyridazin-3(2 H)-ones to a C=C bond with oxygen as the terminal oxidant is described. Functional groups including hydroxy, carboxylic, bromo, chloro, cyano, nitro and alkoxy were all tolerated under the reaction conditions. Moreover, this methodology was applied to the preparation of a series of structurally similar N-substituted 6-phenylpyridazinone compounds containing fluorine. The dehydrogenation reactions exhibit good yields and selectivity. [ABSTRACT FROM AUTHOR]

There is widespread interest in the application, optimization, and evolution of the transition-metal-catalyzed arylation of N-heteroarenes to discover full-color tunable fluorescent core frameworks. Inspired by the versatile roles of pyridazinone in organic synthesis and medicinal chemistry, herein, we report a simple and efficient copper-catalyzed cross-coupling reaction for the N-functionalization of pyridazinones in neat water. To achieve the efficient conversion of pyridazinones and organic halides in aqueous phase, a series of copper-salen complexes composed of different Schiff base ligands were investigated by rational design. A final choice of fine-tuned hydrophilicity balanced with lipophilicity among the candidates was confirmed, which affords excellent activity towards the reaction of a wide range of pyridazinones and organic halides. More importantly, the products as N-substituted pyridazinones were synthesized rationally by this methodology as full-color tunable fluorescent agents (426-612 nm). The N2 position of pyridazinones was modified by different aryl group such as benzothiazole, N, N-dimethylaniline, 3-quinoline, 4-isoquinoline and 2-thiophene, resulting in a series of full-color tunable fluorescent reagents. Meanwhile, the effects of electron-donating and electron-withdrawing groups of the 6-substituted phenyl ring have also been investigated to optimize the fluorescent properties. These fluorescent core frameworks were studied in several cell lines as fluorescent dyes. Different colors from blue to red were observed by using fluorescence microscopy and confocal microscopy. [ABSTRACT FROM AUTHOR]

Preclinical Research As part of a research program to identify compounds with potent antihypertensive properties, a new series of dihydropyridazin ‐ 3(2H) ‐ one analogs was synthesized and evaluated for vasodilator activity in rat thoracic aortic rings. Most of the newly synthesized compounds displayed good vasorelaxant activity as compared with SK&F ‐ 93741 and hydralazine, with the N2 ‐ unsubstituted 4 ‐ isobutyramidophenylpyridazinone derivative 5 being the most potent vasorelaxant, producing vasorelaxation greater than that of hydralazine and equipotent to SK&F ‐ 93741. A significant effect of the 6 ‐ phenyl substituents and substitution at N ‐ 2 position of pyridazinone nucleus on the vasodilatory activity was observed. [ABSTRACT FROM AUTHOR]

ABSTRACT The synthesis of three racemates and the corresponding non-chiral analogues of a C5-methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC-UV were investigated using four chiral stationary phases (CSPs: Lux Amylose-2, Lux Cellulose-1, Lux Cellulose-2 and Lux Cellulose-3). The best resolution was achieved using amylose tris(5-chloro-2-methylphenylcarbamate) (Lux Amylose-2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X-ray crystallographic analysis and comparative chiral HPLC-UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC50 values in the micromolar range. Chirality 25:400-408, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A new series of pyridazinone-based thioderivatives and pyridazine analogs was synthesizedand tested for their ability to bind to the three human formyl peptide receptor (FPR) isoforms (FPR1,FPR2, and FPR3) and to activate intracellular calcium mobilization and chemotaxis in human neutrophils.Among the pyridazin-3(2H)-one derivatives tested, analogs 8b and 8c were mixed FPR1/FPR2 agonists,with median effective concentration values in the micromolar range, and were able to activate chemotaxisand Ca2+ flux in human neutrophils in the low micromolar range. Molecular docking studies showed thatinteraction of a ligand with Arg205 of FPR1 is important for FPR1 agonist activity. For FPR2, differences inactivity between oxygen-containing compounds and their thio-analogs were due to steric bulkiness ofsulfur-containing groups. Drug Dev Res 74 : 259-271, 2013. [ABSTRACT FROM AUTHOR]

A copper-catalyzed cascade dehydrogenative and dehalogenative reaction of halogenated 6-phenyl-4,5-dihydropyridazin-3(2 H)-ones to 6-phenylpyridazin-3(2 H)-ones has been developed. Moreover, the catalytic system consisting of copper(II) acetate/sodium carbonate/pyridine exhibits high reactivity and selectivity with oxygen as the terminal oxidant. [ABSTRACT FROM AUTHOR]

Rh2(OAc)4-Catalyzed decomposition of diazo esters in the presence of perfluoroalkyl- or perfluoroaryl-substituted silyl enol ethers smoothly provided the corresponding alkyl 2-siloxycyclopropanecarboxylates in very good yields. The generated donoracceptor cyclopropanes are equivalents of γ-oxo esters, which we demonstrated by their one-pot transformations to yield fluorine-containing heterocycles. A reductive procedure selectively afforded perfluoroalkyl-substituted γ-hydroxy esters or γ-lactones. The treatment of the donoracceptor cyclopropanes with hydrazine or phenylhydrazine afforded a series of perfluoroalkyl- and perfluoroaryl-substituted 4,5-dihydropyridazin-3(2 H)-ones. [ABSTRACT FROM AUTHOR]

The first one-pot synthesis of pyridazinones and phthalazinones from arenes, cyclic anhydrides, and ArNHNH2 in the presence of efficient recyclable heterogeneous catalyst, HY-zeolite, in high yield and short reaction time is reported. J. Heterocyclic Chem., (2011). [ABSTRACT FROM AUTHOR]

Synthesis of new heterocyclic compounds containing the pyridazinone moiety, which have a valuable biological activities, has been achieved through the nucleophilic addition of benzylamine to 4-(p-substituted phenyl)-4-oxo-2-butenoic acid 1a,b, followed by cyclocondensation of the adducts 2a,b to the corresponding pyridazin-3-one derivatives 3a,b. The behavior of the latter compounds toward different nucleophilic and electrophilic reagents was investigated. The structures of the newly synthesized compounds were elucidated by elemental analysis and spectroscopic data. J. Heterocyclic Chem., (2010). [ABSTRACT FROM AUTHOR]

A series of novel α,α,α-trifluoro-m-tolyl pyridazinone derivatives was synthesised. Herbicidal activities of the two intermediate compounds and 15 pyridazinone derivatives were evaluated through barnyardgrass and rape cup tests and Spirodela polyrrhiza (L.) Schleiden tests. Selected compounds were also evaluated under greenhouse conditions. Bleaching activities were observed at 10 µg ml-1 and some compounds exhibited herbicidal activities at a rate of 300 g ha-1. The relationship between crystal structures and herbicidal activities is discussed through a comparison of two compounds (5a and 5f). [ABSTRACT FROM AUTHOR]

Photoblastic seeds (achenes) of Taraxacum vulgare coll. were treated with a water solution of SAN 9789, 4‐chloro‐5 (methylamino) ‐2‐ (α,α,α‐trifluoro‐m‐tolyl) ‐3(2H) pyridazinone. SAN‐treatment increased the germination in darkness from 0 to 12%. An irradiation for 5 min with red light, giving a germination of 12% for seeds in water only, gave together with SAN treatment a germination of 60%. In both water and SAN, the effect of red irradiation could be reversed by a short irradiation (15 min) of far‐red light. If far‐red light was repeatedly given (5 min per h) it had hardly any effect on germination in water (4% germination), but for seeds in SAN solution, intermittent far‐red light had a stimulating effect (63% germination). If far‐red light was given continuously for 96 h, the germination in water was 1% and in SAN solution 17%. The results in the present paper indicate that SAN may broaden the concentration interval of Pfr for which germination is high. [ABSTRACT FROM AUTHOR]

The effects of norflurazon (San 9789) on light-increased extractable NADH nitrate reductase activity (NRA) in soybean seedlings were studied. Continuous white light (W) increased NRA steadily in root and cotyledonary tissues over a 5 d period. Norflurazon, a pyridazinone herbicide which causes chlorophyll bleaching in W, reduced the initial NRA induction rate in roots and cotyledons. However, in cotyledons of norflurazon-treated plants NRA increased at a more rapid rate than in the control after 24 h of W, with activity levels reaching three times those of control seedlings alter 5 d. NRA induced by W in control and norflurazon-treated cotyledons was fluence-rate dependent. Continuous FR induced equal amounts of NRA in control and norflurazon-treated tissues, suggesting that the superinduceable NRA of norflurazon-treated plants under W is not phytochrome induced. The FR-induced NRA of control and norflurazon-treated cotyledons had pH optima of 6.6, but during development under W the pH optimum of control cotyledons changed from 6.3 to between 6.6 and 7.1. The pH optimum of the norflurazon-induced NRA of the cotyledon under W was about 7.5. The NADH/NADPH NRA ratio after 4 d of W was 1.3 in control and 2.5 in norflurazon-treated cotyledons. These data indicate that photosynthetic pigments are involved only secondarily in light-induction of NRA in this system. [ABSTRACT FROM AUTHOR]

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Copyright of Weed Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

1. From the culture me,urn of bacteria, which utilize 5-amino-4-chloro-2-phenyl-3(2H)pyridazinone (pyrazon) as sole source of carbon four metabolites could be isolated. These metabolites were identified as 5-amino-4-chloro-2-(2,3-cis-dihydroxycyclohexa-4,6-diene-1-yl)-3(2H)pyridazinone (compound I), as 2-(5-amino-4-chloro-3-oxo-2,3-dihydro-2-pyridazino)-cis,cismuconic acid (compound II), as 2-pyrone-6-carboxylic acid (compound III) and as 5-amino-4-chloro-3(2H)-pyridazinone (compound IV). 2. Cell-free extracts of the pyrazon-degrading bacteria were shown to metabolize 2-hydroxymuconic acid with a stoichiometric release of CO2. 3. A pathway for the bacterial degradation of 5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone is proposed. [ABSTRACT FROM AUTHOR]

Copyright of Weed Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Weed Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cover Feature: Isomerisation of Vinyl Sulfones for the Stereoselective Synthesis of Vinyl Azides (Eur. J. Org. B The Cover Feature b shows a kinetically controlled process where Green represents "go to Z (cis)" and Red represents "don't go to E (trans)" for the isomerisation of a series of 3-azido E-vinyl sulfones. This process has been studied, and on treatment with the base DBU it has been found that, for most structural variations, these vinyl sulfones selectively generate Z-vinyl azides. [Extracted from the article]

Chemical equations for the article "Expedient Synthesis of New Cinnoline Diones by Ru-Catalyzed Regioselective Unexpected Deoxygenation-Oxidative Annulation of Propargyl Alcohols with Phthalazinones and Pyridazinones" by S. Rajkumar and others, published in the "Chemical Communications" in 2016.

Review: 190 refs. [ABSTRACT FROM AUTHOR]

2-Acyloxypyridazinone is utilized as heterocycle-based acyl-transfer agent in various acylation reactions. [ABSTRACT FROM AUTHOR]

The tandem reaction of hydrazide (I) with ketone (II) proceeds in the presence of excess NaHCO3 to give the title products (III) containing three new rings. [ABSTRACT FROM AUTHOR]

The article discusses Primary and Secondary Amines and Access to Pyridazinones and Triazinones with Divergent Reactivity of N-Isocyanates.